Frontiers of Medicine

, Volume 13, Issue 3, pp 298–313 | Cite as

HLA and lung transplantation

  • Liya JuEmail author
  • Caroline Suberbielle
  • Xiaofan Li
  • Nuala Mooney
  • Dominique Charron


Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.


human leukocyte antigen class I and II lung transplantation mismatch obliterans bronchiolitis alloantibody antibody mediated rejection 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Dobbels F, Goldfarb SB, Levvey BJ, Lund LH, Meiser B, Stehlik J; International Society for Heart and Lung Transplantation. The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant 2014; 33(10): 1009–1024Google Scholar
  2. 2.
    Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients(SRTR). OPTN/SRTR 2010 Annual Data Report. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, 2011Google Scholar
  3. 3.
    Levine DJ, Glanville AR, Aboyoun C, Belperio J, Benden C, Berry GJ, Hachem R, Hayes D Jr, Neil D, Reinsmoen NL, Snyder LD, Sweet S, Tyan D, Verleden G, Westall G, Yusen RD, Zamora M, Zeevi A. Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2016; 35(4): 397–406Google Scholar
  4. 4.
    McManigle W, Pavlisko EN, Martinu T. Acute cellular and antibody-mediated allograft rejection. Semin Respir Crit Care Med 2013; 34(3): 320–335Google Scholar
  5. 5.
    Auffray C, Charron D, Hood L. Predictive, preventive, personalized and participatory medicine: back to the future. Genome Med 2010; 2(8): 57Google Scholar
  6. 6.
    Robinson J, Halliwell JA, Hayhurst JH, Flicek P, Parham P, Marsh SGE. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res 2015;43(Database issue):D423–431Google Scholar
  7. 7.
    Wisser W, Wekerle T, Zlabinger G, Senbaclavaci O, Zuckermann A, Klepetko W, Wolner E. Influence of human leukocyte antigen matching on long-term outcome after lung transplantation. J Heart Lung Transplant 1996; 15(12): 1209–1216Google Scholar
  8. 8.
    Smits JMA, Mertens BJA, Van Houwelingen HC, Haverich A, Persijn GG, Laufer G. Predictors of lung transplant survival in eurotransplant. Am J Transplant 2003; 3(11): 1400–1406Google Scholar
  9. 9.
    Quantz MA, Bennett LE, Meyer DM, Novick RJ. Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations. J Heart Lung Transplant 2000; 19(5): 473–479Google Scholar
  10. 10.
    Wong JY, Tait B, Levvey B, Griffiths A, Esmore DS, Snell GI, Williams TJ, Kotsimbos TC. Epstein-Barr virus primary mismatching and HLA matching: key risk factors for post lung transplant lymphoproliferative disease. Transplantation 2004; 78(2): 205–210Google Scholar
  11. 11.
    Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ, van der Heide JJ, Lems SP, Veeger NJ, Kluin PM, Kluin-Nelemans HC, Hepkema BG. HLA antigens and post renal transplant lymphoproliferative disease: HLA-B matching is critical. Transplantation 2005; 80(5):595–599Google Scholar
  12. 12.
    Opelz G, Süsal C, Ruhenstroth A, Döhler B. Impact of HLA compatibility on lung transplant survival and evidence for an HLA restriction phenomenon: a collaborative transplant study report. Transplantation 2010; 90(8): 912–917Google Scholar
  13. 13.
    Hayes D Jr, Whitson BA, Ghadiali SN, Tobias JD, Mansour HM, Black SM. Influence of HLA mismatching on survival in lung transplantation. Lung 2015; 193(5): 789–797Google Scholar
  14. 14.
    Hayes D Jr, Black SM, Tobias JD, Kopp BT, Kirkby SE, Mansour HM, Whitson BA. Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation. J Heart Lung Transplant 2016; 35(2):186–194Google Scholar
  15. 15.
    Harjula AL, Baldwin JC, Glanville AR, Tazelaar H, Oyer PE, Stinson EB, Shumway NE. Human leukocyte antigen compatibility in heart-lung transplantation. J Heart Transplant 1987; 6(3): 162–166Google Scholar
  16. 16.
    Sundaresan S, Mohanakumar T, Smith MA, Trulock EP, Lynch J, Phelan D, Cooper JD, Patterson GA. HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome. Transplantation 1998; 65(5): 648–653Google Scholar
  17. 17.
    Brugière O, Thabut G, Suberbielle C, Reynaud-Gaubert M, Thomas P, Pison C, Saint Raymond C, Mornex JF, Bertocchi M, Dromer C, Velly JF, Stern M, Philippe B, Dauriat G, Biondi G, Castier Y, Fournier M. Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation. J Heart Lung Transplant 2008; 27(6): 628–634Google Scholar
  18. 18.
    Peltz M, Bennett Edwards L, Jessen ME, Torres F, Meyer DM. Impact of HLA class I and class II mismatching on lung transplant recipient mortality, rejection, and bronchiolitis obliterans. J Heart Lung Transplant 2006; 25(suppl): S112Google Scholar
  19. 19.
    Chalermskulrat W, Neuringer IP, Schmitz JL, Catellier DJ, Gurka MJ, Randell SH, Aris RM. Human leukocyte antigen mismatches predispose to the severity of bronchiolitis obliterans syndrome after lung transplantation. Chest 2003; 123(6): 1825–1831Google Scholar
  20. 20.
    Schulman LL, Weinberg AD, McGregor C, Galantowicz ME, Suciu-Foca NM, Itescu S. Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation. Am J Respir Crit Care Med 1998; 157(6 Pt 1): 1833–1837Google Scholar
  21. 21.
    Iwaki Y, Yoshida Y, Griffith B. The HLA matching effect in lung transplantation. Transplantation 1993; 56(6): 1528–1564Google Scholar
  22. 22.
    Love RB, Meyer KC, Devito-Haynes LD, Ulschmid S, Leverson GE, Van Der Bij W, De Boer WJ, Hepkema BG, Cornwell RD, Woolley DS, Burlingham WJ. Effect of HLA-DR mismatch on lung transplant outcome. J Heart Lung Transplant 2001; 20(2): 177Google Scholar
  23. 23.
    Wan L, Chen DF. The influence of HLA antigen mismatch and epitope mismathe on lung transplant survival: analysis of OPTN data after LAS allocation. Hum Immunol 2015; 76: 124–167Google Scholar
  24. 24.
    Butts RJ, Savage AJ, Nietert PJ, Kavarana M, Moussa O, Burnette AL, Atz AM. Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival. J Heart Lung Transplant 2014; 33(12): 1282–1287Google Scholar
  25. 25.
    Afzali B, Lombardi G, Lechler RI. Pathways of major histocompatibility complex allorecognition. Curr Opin Organ Transplant 2008; 13(4): 438–444Google Scholar
  26. 26.
    Herrera OB, Golshayan D, Tibbott R, Salcido Ochoa F, James MJ, Marelli-Berg FM, Lechler RI. A novel pathway of alloantigen presentation by dendritic cells. J Immunol 2004; 173(8): 4828–4837Google Scholar
  27. 27.
    Shilling RA, Wilkes DS. Immunobiology of chronic lung allograft dysfunction: new insights from the bench and beyond. Am J Transplant 2009; 9(8): 1714–1718Google Scholar
  28. 28.
    Hachem RR. Lung allograft rejection: diagnosis and management. Curr Opin Organ Transplant 2009;14(5):477–482Google Scholar
  29. 29.
    Pober JS, Jane-wit D, Qin L, Tellides G. Interacting mechanisms in the pathogenesis of cardiac allograft vasculopathy. Arterioscler Thromb Vasc Biol 2014; 34(8): 1609–1614Google Scholar
  30. 30.
    DeNicola MM, Weigt SS, Belperio JA, Reed EF, Ross DJ, Wallace WD. Pathologic findings in lung allografts with anti-HLA antibodies. J Heart Lung Transplant 2013; 32(3): 326–332Google Scholar
  31. 31.
    Visentin J, Chartier A, Massara L, Linares G, Guidicelli G, Blanchard E, Parrens M, Begueret H, Dromer C, Taupin JL. Lung intragraft donor-specific antibodies as a risk factor for graft loss. J Heart Lung Transplant 2016; 35(12): 1418–1426Google Scholar
  32. 32.
    Hachem R. Antibody-mediated lung transplant rejection. Curr Respir Care Rep 2012; 1(3): 157–161Google Scholar
  33. 33.
    2004 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1994–2003. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD; United Network for Organ Sharing, Richmond, VA; University Renal Research and Education Association, Ann Arbor, MIGoogle Scholar
  34. 34.
    Lau CL, Palmer SM, Posther KE, Howell DN, Reinsmoen NL, Massey HT, Tapson VF, Jaggers JJ, D’Amico TA, Davis RD Jr. Influence of panel-reactive antibodies on posttransplant outcomes in lung transplant recipients. Ann Thorac Surg 2000; 69(5): 1520–1524Google Scholar
  35. 35.
    Shah AS, Nwakanma L, Simpkins C, Williams J, Chang DC, Conte JV. Pretransplant panel reactive antibodies in human lung transplantation: an analysis of over 10,000 patients. Ann Thorac Surg 2008; 85(6): 1919–1924Google Scholar
  36. 36.
    Mangi AA, Mason DP, Nowicki ER, Batizy LH, Murthy SC, Pidwell DJ, Avery RK, McCurry KR, Pettersson GB, Blackstone EH. Predictors of acute rejection after lung transplantation. Ann Thorac Surg 2011; 91(6): 1754–1762Google Scholar
  37. 37.
    Hirche TO, Knoop C, Hebestreit H. Practical guidelines: lung transplantation in patients with cystic fibrosis. Pulm Med 2014; 2014:621342Google Scholar
  38. 38.
    Choi JK, Kearns J, Palevsky HI, Montone KT, Kaiser LR, Zmijewski CM, Tomaszewski JE. Hyperacute rejection of a pulmonary allograft. Immediate clinical and pathologic findings. Am J Respir Crit Care Med 1999; 160(3): 1015–1018Google Scholar
  39. 39.
    Frost AE, Jammal CT, Cagle PT. Hyperacute rejection following lung transplantation. Chest 1996; 110(2): 559–562Google Scholar
  40. 40.
    Bittner HB, Dunitz J, Hertz M, Bolman MR 3rd, Park SJ. Hyperacute rejection in single lung transplantation—case report of successful management by means of plasmapheresis and antithymocyte globulin treatment. Transplantation 2001; 71(5): 649–651Google Scholar
  41. 41.
    Masson E, Stern M, Chabod J, Thévenin C, Gonin F, Rebibou JM, Tiberghien P. Hyperacute rejection after lung transplantation caused by undetected low-titer anti-HLA antibodies. J Heart Lung Transplant 2007; 26(6): 642–645Google Scholar
  42. 42.
    Loupy A, Lefaucheur C, Vernerey D, Prugger C, Duong van Huyen JP, Mooney N, Suberbielle C, Frémeaux-Bacchi V, Méjean A, Desgrandchamps F, Anglicheau D, Nochy D, Charron D, Empana JP, Delahousse M, Legendre C, Glotz D, Hill GS, Zeevi A, Jouven X. Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med 2013; 369(13): 1215–1226Google Scholar
  43. 43.
    Sicard A, Ducreux S, Rabeyrin M, Couzi L, McGregor B, Badet L, Scoazec JY, Bachelet T, Lepreux S, Visentin J, Merville P, Fremeaux-Bacchi V, Morelon E, Taupin JL, Dubois V, Thaunat O. Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss. J Am Soc Nephrol 2015; 26(2): 457–467Google Scholar
  44. 44.
    Tambur AR, Claas FH. HLA epitopes as viewed by antibodies: what is it all about? Am J Transplant 2015; 15(5): 1148–1154Google Scholar
  45. 45.
    Zhang Q, Cecka JM, Gjertson DW, Ge P, Rose ML, Patel JK, Ardehali A, Kobashigawa JA, Fishbein MC, Reed EF. HLA and MICA: targets of antibody-mediated rejection in heart transplantation. Transplantation 2011; 91(10): 1153–1158Google Scholar
  46. 46.
    Hachem RR, Yusen RD, Meyers BF, Aloush AA, Mohanakumar T, Patterson GA, Trulock EP. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant 2010; 29(9): 973–980Google Scholar
  47. 47.
    Lobo LJ, Aris RM, Schmitz J, Neuringer IP. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant 2013; 32(1): 70–77Google Scholar
  48. 48.
    Snyder LD, Wang Z, Chen DF, Reinsmoen NL, Finlen-Copeland CA, Davis WA, Zaas DW, Palmer SM. Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients. Chest 2013; 144(1): 226–233Google Scholar
  49. 49.
    Girnita AL, McCurry KR, Iacono AT, Duquesnoy R, Corcoran TE, Awad M, Spichty KJ, Yousem SA, Burckart G, Dauber JH, Griffith BP, Zeevi A. HLA-specific antibodies are associated with highgrade and persistent-recurrent lung allograft acute rejection. J Heart Lung Transplant 2004; 23(10): 1135–1141Google Scholar
  50. 50.
    Palmer SM, Davis RD, Hadjiliadis D, Hertz MI, Howell DN, Ward FE, Savik K, Reinsmoen NL. Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Transplantation 2002; 74(6): 799–804Google Scholar
  51. 51.
    Trulock EP, Christie JD, Edwards LB, Boucek MM, Aurora P, Taylor DO, Dobbels F, Rahmel AO, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart-lung transplantation report—2007. J Heart Lung Transplant 2007; 26(8): 782–795Google Scholar
  52. 52.
    Tait BD, Süsal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, Reed EF, Bray RA, Campbell P, Chapman JR, Coates PT, Colvin RB, Cozzi E, Doxiadis II, Fuggle SV, Gill J, Glotz D, Lachmann N, Mohanakumar T, Suciu-Foca N, Sumitran-Holgersson S, Tanabe K, Taylor CJ, Tyan DB, Webster A, Zeevi A, Opelz G. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 2013; 95(1): 19–47Google Scholar
  53. 53.
    Jaramillo A, Smith MA, Phelan D, Sundaresan S, Trulock EP, Lynch JP, Cooper JD, Patterson GA, Mohanakumar T. Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation. Transplantation 1999; 67(8): 1155–1161Google Scholar
  54. 54.
    Girnita AL, Duquesnoy R. Yousem SA, Iacono AT, Corcoran TE, Buzoianu M, Johnson B, Spichty KJ, Dauber JH, Burckart G, Griffith BP, McCurry KR, Zeevi A. HLA-specific antibodies are risk factors forlymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant 2005; 5: 131–138Google Scholar
  55. 55.
    Cardarelli F, Pascual M, Tolkoff-Rubin N, Delmonico FL, Wong W, Schoenfeld DA, Zhang H, Cosimi AB, Saidman SL. Prevalence and significance of anti-HLA and donor-specific antibodies longterm after renal transplantation. Transpl Int 2005; 18(5): 532–540Google Scholar
  56. 56.
    Lachmann N, Terasaki PI, Schönemann C. Donor-specific HLA antibodies in chronic renal allograft rejection: a prospective trial with a four-year follow-up. Clin Transpl 2006; 2006:171–199Google Scholar
  57. 57.
    Otten HG, Verhaar MC, Borst HP, Hené RJ, van Zuilen AD. Pretransplant donor-specific HLA class-I and -II antibodies are associated with an increased risk for kidney graft failure. Am J Transplant 2012; 12(6): 1618–1623Google Scholar
  58. 58.
    Reznik SI, Jaramillo A, Zhang L, Patterson GA, Cooper JD, Mohanakumar T. Anti-HLA antibody binding to HLA class I molecules induces proliferation of airway epithelial cells: a potential mechanism for bronchiolitis obliterans syndrome. J Thorac Cardiovasc Surg 2000; 119(1): 39–45Google Scholar
  59. 59.
    Kim M, Townsend KR, Wood IG, Boukedes S, Guleria I, Gabardi S, El-Chemaly S, Camp PC, Chandraker AK, Milford EL, Goldberg HJ. Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates. Am J Respir Crit Care Med 2014; 189(10): 1234–1239Google Scholar
  60. 60.
    Wiebe C, Pochinco D, Blydt-Hansen TD, Ho J, Birk PE, Karpinski M, Goldberg A, Storsley LJ, Gibson IW, Rush DN, Nickerson PW. Class II HLA epitope matching—a strategy to minimize de novo donor-specific antibody development and improve outcomes. Am J Transpl 2013; 13: 3114–3122Google Scholar
  61. 61.
    Colvin RB. Antibody-mediated renal allograft rejection: diagnosis and pathogenesis. J Am Soc Nephrol 2007; 18(4): 1046–1056Google Scholar
  62. 62.
    Song EY, Lee YJ, Hyun J, Kim YS, Ahn C, Ha J, Kim SJ, Park MH. Clinical relevance of pretransplant HLA class II donorspecific antibodies in renal transplantation patients with negative Tcell cytotoxicity crossmatches. Ann Lab Med 2012; 32(2): 139–144Google Scholar
  63. 63.
    Bieri M, Oroszlan M, Farkas A, Ligeti N, Bieri J, Mohacsi P. Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability. Int J Biochem Cell Biol 2009; 41(12): 2422–2430Google Scholar
  64. 64.
    Lefaucheur C, Loupy A, Hill GS, Andrade J, Nochy D, Antoine C, Gautreau C, Charron D, Glotz D, Suberbielle-Boissel C. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 2010; 21(8): 1398–1406Google Scholar
  65. 65.
    Lefaucheur C, Antoine C, Suberbielle C, Glotz D. Mastering the risk of HLA antibodies in kidney transplantation: an algorithm based on pretransplant single-antigen flow bead techniques. Am J Transplant 2011; 11(8): 1592–1598Google Scholar
  66. 66.
    Safavi S, Robinson DR, Soresi S, Carby M, Smith JD. De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2014; 33(12): 1273–1281Google Scholar
  67. 67.
    Witt CA, Gaut JP, Yusen RD, Byers DE, Iuppa JA, Bennett Bain K, Alexander Patterson G, Mohanakumar T, Trulock EP, Hachem RR. Acute antibody-mediated rejection after lung transplantation. J Heart Lung Transplant 2013; 32(10): 1034–1040Google Scholar
  68. 68.
    Smith JD, Banner NR, Hamour IM, Ozawa M, Goh A, Robinson D, Terasaki PI, Rose ML. De novo donor HLA-specific antibodies after heart transplantation are an independent predictor of poor patient survival. Am J Transplant 2011; 11(2): 312–319Google Scholar
  69. 69.
    Roux A, Bendib Le Lan I, Holifanjaniaina S, Thomas KA, Hamid AM, Picard C, Grenet D, De Miranda S, Douvry B, Beaumont-Azuar L, Sage E, Devaquet J, Cuquemelle E, Le Guen M, Spreafico R, Suberbielle-Boissel C, Stern M, Parquin F; Foch Lung Transplantation Group. Antibody-mediated rejection in lung transplantation: clinical outcomes and donor-specific antibody characteristics. Am J Transplant 2016; 16(4): 1216–1228Google Scholar
  70. 70.
    Kopchaliiska D, Kukreja J, Dincheva G, Bush E, Leard L, Singer J, Brzezinski M, Hays S, Rajalingam R. IVIG infusion deplete donorspecific HLA antibodies in lung transplant recipients: a singlecenter experience. Hum Immunol 2015; 76(Suppl): 14–37Google Scholar
  71. 71.
    Stern M, Hirsch H, Cusini A, van Delden C, Manuel O, Meylan P, Boggian K, Mueller NJ, Dickenmann M; Members of Swiss Transplant Cohort Study. Cytomegalovirus serology and replication remain associated with solid organ graft rejection and graft loss in the era of prophylactic treatment. Transplantation 2014; 98(9): 1013–1018Google Scholar
  72. 72.
    Baxter-Lowe L, Singer J, Hays S, Kukreja J, Golden J, Leard L. Late after lung transplantation many patients have donor-specific HLA antibodies (DSA) and high DSA levels appear to be associated with poor outcomes. Am J Transplant 2013; 13 (suppl 5) [abstract]Google Scholar
  73. 73.
    Zeevi A, Marrari M, Spichty K, Morrell M, Gries C, McDyer J, Pilewski J, Zaldonis D, Bhama J, Shigemura N, Yousem S, Duquesnoy R, D’Cunha J, Bermudez C. Increased frequency of class II HLA-DQ donor-specific antibodies is associated with mixed cellular and humoral rejection in lungtransplantation. J Heart Lung Transplant 2013; 32(4 4S): S76Google Scholar
  74. 74.
    Tikkanen JM, Singer LG, Kim SJ, Li Y, Binnie M, Chaparro C, Chow CW, Martinu T, Azad S, Keshavjee S, Tinckam K. De novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med 2016; 194(5): 596–606Google Scholar
  75. 75.
    Loupy A, Lefaucheur C, Vernerey D, Prugger C, Duong van Huyen JP, Mooney N, Suberbielle C, Frémeaux-Bacchi V, Méjean A, Desgrandchamps F, Anglicheau D, Nochy D, Charron D, Empana JP, Delahousse M, Legendre C, Glotz D, Hill GS, Zeevi A, Jouven X. Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med 2013; 369(13): 1215–1226Google Scholar
  76. 76.
    Yell M, Muth BL, Kaufman DB, Djamali A, Ellis TM. C1q binding activity of de novo donor-specific HLA antibodies in renal transplant recipients with and without antibody-mediated rejection. Transplantation 2015; 99(6): 1151–1155Google Scholar
  77. 77.
    Sicard A, Ducreux S, Rabeyrin M, Couzi L, McGregor B, Badet L, Scoazec JY, Bachelet T, Lepreux S, Visentin J, Merville P, Fremeaux-Bacchi V, Morelon E, Taupin JL, Dubois V, Thaunat O. Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss. J Am Soc Nephrol 2015; 26(2): 457–467Google Scholar
  78. 78.
    Strainic MG, Liu J, Huang D, An F, Lalli PN, Muqim N, Shapiro VS, Dubyak GR, Heeger PS, Medof ME. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 2008; 28(3): 425–435Google Scholar
  79. 79.
    Westall GP, Snell GI, McLean C, Kotsimbos T,Williams T, Magro C. C3d and C4d deposition early after lung transplantation. J Heart Lung Transplant 2008; 27(7): 722–728Google Scholar
  80. 80.
    Lepin EJ, Zhang Q, Zhang X, Jindra PT, Hong LS, Ayele P, Peralta MV, Gjertson DW, Kobashigawa JA, Wallace WD, Fishbein MC, Reed EF. Phosphorylated S6 ribosomal protein: a novel biomarker of antibody-mediated rejection in heart allografts. Am J Transplant 2006; 6(7): 1560–1571Google Scholar
  81. 81.
    Hirohashi T, Chase CM, Della Pelle P, Sebastian D, Alessandrini A, Madsen JC, Russell PS, Colvin RB. A novel pathway of chronic allograft rejection mediated by NK cells and alloantibody. Am J Transplant 2012; 12(2): 313–321Google Scholar
  82. 82.
    Zhang X, Reed EF. Effect of antibodies on endothelium. Am J Transplant 2009; 9(11): 2459–2465Google Scholar
  83. 83.
    Li F,Wei J, Valenzuela NM, Lai C, Zhang Q, Gjertson D, Fishbein MC, Kobashigawa JA, Deng M, Reed EF. Phosphorylated S6 kinase and S6 ribosomal protein are diagnostic markers of antibody-mediated rejection in heart allografts. J Heart Lung Transplant 2015; 34(4): 580–587Google Scholar
  84. 84.
    Le Bas-Bernardet S, Coupel S, Chauveau A, Soulillou JP, Charreau B. Vascular endothelial cells evade apoptosis triggered by human leukocyte antigen-DR ligation mediated by allospecific antibodies. Transplantation 2004; 78(12): 1729–1739Google Scholar
  85. 85.
    Lion J, Taflin C, Cross AR, Robledo-Sarmiento M, Mariotto E, Savenay A, Carmagnat M, Suberbielle C, Charron D, Haziot A, Glotz D, Mooney N. HLA class II antibody activation of endothelial cells promotes Th17 and disrupts regulatory T lymphocyte expansion. Am J Transplant 2016; 16(5): 1408–1420Google Scholar
  86. 86.
    Deteix C, Attuil-Audenis V, Duthey A, Patey N, McGregor B, Dubois V, Caligiuri G, Graff-Dubois S, Morelon E, Thaunat O. Intragraft Th17 infiltrate promotes lymphoid neogenesis and hastens clinical chronic rejection. J Immunol 2010; 184(9): 5344–5351Google Scholar
  87. 87.
    Basha HI, Ramachandran S, Tiriveedhi V, Takenaka M, Sub-ramanian V, Nath DS, Benshoff N, Patterson GA, Mohanakumar T. Critical role for IL-17A/F in the immunopathogenesis of obliterative airway disease induced by anti-MHC I antibodies. Transplantation 2013; 95(2): 293–300Google Scholar
  88. 88.
    Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and complement promote T cell-mediated cardiac allograft vasculopathy through noncanonical nuclear factor-kB signaling in endothelial cells. Circulation 2013; 128(23): 2504–2516Google Scholar
  89. 89.
    Mezzetti M, Soloperto M, Fasoli A, Mattoli S. Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophages. J Allergy Clin Immunol 1991; 87(5): 930–938Google Scholar
  90. 90.
    Cunningham AC, Zhang JG, Moy JV, Ali S, Kirby JA. A comparison of the antigen-presenting capabilities of class II MHCexpressing human lung epithelial and endothelial cells. Immunology 1997; 91(3): 458–463Google Scholar
  91. 91.
    Hidalgo LG, Sellares J, Sis B, Mengel M, Chang J, Halloran PF. Interpreting NK cell transcripts versus T cell transcripts in renal transplant biopsies. Am J Transplant 2012; 12(5): 1180–1191Google Scholar
  92. 92.
    Parkes MD, Halloran PF, Hidalgo LG. Evidence for CD16amediated NK cell stimulation in antibody-mediated kidney transplant rejection. Transplantation 2017; 101(4): e102–e111Google Scholar
  93. 93.
    Saini D, Angaswamy N, Tiriveedhi V, Fukami N, Ramachandran S, Hachem R, Trulock E, Meyers B, Patterson A, Mohanakumar T. Synergistic effect of antibodies to human leukocyte antigens and defensins in pathogenesis of bronchiolitis obliterans syndrome after human lung transplantation. J Heart Lung Transplant 2010; 29(12): 1330–1336Google Scholar
  94. 94.
    Fukami N, Ramachandran S, Saini D, Walter M, Chapman W, Patterson GA, Mohanakumar T. Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol 2009; 182(1): 309–318Google Scholar
  95. 95.
    Jaramillo A, Smith CR, Maruyama T, Zhang L, Patterson GA, Mohanakumar T. Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: a possible mechanism for bronchiolitis obliterans syndrome. Hum Immunol 2003; 64(5): 521–529Google Scholar
  96. 96.
    Hill GS, Nochy D, Bruneval P, Duong van Huyen JP, Glotz D, Suberbielle C, Zuber J, Anglicheau D, Empana JP, Legendre C, Loupy A. Donor-specific antibodies accelerate arteriosclerosis after kidney transplantation. J Am Soc Nephrol 2011; 22(5): 975–983Google Scholar
  97. 97.
    Maruyama T, Jaramillo A, Narayanan K, Higuchi T, Mohanakumar T. Induction of obliterative airway disease by anti-HLA class I antibodies. Am J Transplant 2005; 5(9): 2126–2134Google Scholar
  98. 98.
    Yamada Y, Sekine Y, Yoshida S, Yasufuku K, Petrache I, Benson HL, Brand DD, Yoshino I, Wilkes DS. Type V collagen-induced oral tolerance plus low-dose cyclosporine prevents rejection of MHC class I and II incompatible lung allografts. J Immunol 2009; 183(1): 237–245Google Scholar
  99. 99.
    Xu Z, Nayak DK, Benshoff N, Hachem R, Gelman AE, Mohanakumar T. De novo-developed antibodies to donor MHC antigens lead to dysregulation of microRNAs and induction of MHC class II. J Immunol 2015; 194(12): 6133–6143Google Scholar
  100. 100.
    Nayak DK, Zhou F, Xu M, Huang J, Tsuji M, Yu J, Hachem R, Gelman AE, Bremner RM, Smith MA, Mohanakumar T. Zbtb7a induction in alveolar macrophages is implicated in anti-HLAmediated lung allograft rejection. Sci Transl Med 2017; 9(398): eaal1243Google Scholar
  101. 101.
    Otani S, Davis AK, Cantwell L, Ivulich S, Pham A, Paraskeva MA, Snell GI, Westall GP. Evolving experience of treating antibodymediated rejection following lung transplantation. Transpl Immunol 2014; 31(2): 75–80Google Scholar
  102. 102.
    Rodey GE, Fuller TC. Public epitopes and the antigenic structure of the HLA molecules. Crit Rev Immunol 1987; 7(3): 229–267Google Scholar
  103. 103.
    Ayala García MA, González Yebra B, López Flores AL, Guaní Guerra E. The major histocompatibility complex in transplantation. J Transplant 2012; 2012: 842141Google Scholar
  104. 104.
    Opelz G, Mytilineos J, Scherer S, Dunckley H, Trejaut J, Chapman J, Middleton D, Savage D, Fischer O, Bignon JD, Bensa JC, Albert E, Noreen H; The Collaborative Transplant Study. Survival of DNA HLA-DR typed and matched cadaver kidney transplants. Lancet 1991; 338(8765): 461–463Google Scholar
  105. 105.
    Takemoto SK, Terasaki PI, Gjertson DW, Cecka JM. Twelve years’ experience with national sharing of HLA-matched cadaveric kidneys for transplantation. N Engl J Med 2000; 343(15): 1078–1084Google Scholar
  106. 106.
    Rubinstein P. HLA matching for bone marrow transplantation— how much is enough? N Engl J Med 2001; 345(25): 1842–1844Google Scholar
  107. 107.
    Kawase T, Matsuo K, Kashiwase K, Inoko H, Saji H, Ogawa S, Kato S, Sasazuki T, Kodera Y, Morishima Y; Japan Marrow Donor Program. HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism. Blood 2009; 113: 2851–2858Google Scholar
  108. 108.
    Chin N, Paraskeva M, Paul E, Cantwell L, Levvey B, Williams T, Snell G, Westall G. Comparative analysis of how immune sensitization is defined prior to lung transplantation. Hum Immunol 2015; 76(10): 711–716Google Scholar
  109. 109.
    Burton CM, Iversen M, Milman N, Zemtsovski M, Carlsen J, Steinbrüchel D, Mortensen J, Andersen CB. Outcome of lung transplanted patients with primary graft dysfunction. Eur J Cardiothorac Surg 2007; 31(1): 75–82Google Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Liya Ju
    • 1
    Email author
  • Caroline Suberbielle
    • 2
  • Xiaofan Li
    • 3
  • Nuala Mooney
    • 3
    • 4
  • Dominique Charron
    • 1
    • 2
    • 4
    • 5
  1. 1.HLA et Medecine, “Jean Dausset” Laboratory NetworkHôpital Saint-LouisParisFrance
  2. 2.Laboratoire HistocompatibilitéHôpital Saint-LouisParisFrance
  3. 3.INSERM U1160, Hôpital Saint-LouisUniversité Paris DiderotSorbonne Paris CitéFrance
  4. 4.Labex TransplantexStrasbourgFrance
  5. 5.Shanghai Jiao Tong University School of MedicineShanghaiChina

Personalised recommendations